Labor and skills gap analysis of the biomedical research workforce.

The United States has experienced an unsustainable increase of the biomedical research workforce over the past 3 decades. This expansion has led to a myriad of consequences, including an imbalance in the number of researchers and available tenure-track faculty positions, extended postdoctoral training periods, increasing age of investigators at first U.S.

Endothelial cell tube formation assay for the in vitro study of angiogenesis.

Angiogenesis is a vital process for normal tissue development and wound healing, but is also associated with a variety of pathological conditions. Using this protocol, angiogenesis may be measured in vitro in a fast, quantifiable manner. Primary or immortalized endothelial cells are mixed with conditioned media and plated on basement membrane matrix.

Future directions for postdoctoral training in cancer prevention: insights from a panel of experts.

Cancer prevention postdoctoral fellowships have existed since the 1970s. The National Cancer Institute facilitated a meeting by a panel of experts in April 2013 to consider four important topics for future directions for cancer prevention postdoctoral training programs: (i) future research needs; (ii) underrepresented disciplines; (iii) curriculum; and (iv) career preparation. Panelists proffered several areas needing more research or emphasis, ranging from computational science to culture.

Tpl2 knockout keratinocytes have increased biomarkers for invasion and metastasis.

Skin cancer is the most common form of cancer in the USA, with an estimated two million cases diagnosed annually. Tumor progression locus 2 (Tpl2), also known as MAP3K8, is a serine/threonine protein kinase in the mitogen-activated protein kinase signal transduction cascade. Tpl2 was identified by our laboratory as having a tumor suppressor function in skin carcinogenesis, with the absence of this gene contributing to heightened inflammation and increased skin carcinogenesis.

TUSC1, a putative tumor suppressor gene, reduces tumor cell growth in vitro and tumor growth in vivo.

We previously reported the identification of TUSC1 (Tumor Suppressor Candidate 1), as a novel intronless gene isolated from a region of homozygous deletion at D9S126 on chromosome 9p in human lung cancer. In this study, we examine the differential expression of TUSC1 in human lung cancer cell lines by western blot and in a primary human lung cancer tissue microarray by immunohistochemical analysis. We also tested the functional activities and mechanisms of TUSC1 as a tumor suppressor gene through growth suppression in vitro and in vivo.

Altered prostanoid signaling contributes to increased skin tumorigenesis in Tpl2 knockout mice.

Squamous cell carcinoma is the second most common form of skin cancer with the incidence expected to double over the next 20 years. Inflammation is believed to be a critical component in skin cancer progression. Therefore, understanding genes involved in the regulation of inflammatory pathways is vital to the design of targeted therapies.

Outcome evaluation of the National Cancer Institute career development awards program.

The National Cancer Institute (NCI) career development (K) awards program supports investigators to develop their cancer research programs and achieve independence. The NCI Center for Cancer Training conducted a K program evaluation by analyzing outcomes of awardees and individuals who applied to the program but were not funded. The evaluation covered seven NCI mechanisms (K01, K07, K08, K11, K22, K23, and K25) between 1980 and 2008.

Expanding cancer prevention education to national and international audiences: the National Cancer Institute's Principles and Practice of Cancer Prevention and Control annual summer course.

The Summer Curriculum in Cancer Prevention has been sponsored by the National Cancer Institute's Cancer Prevention Fellowship Program for over two decades. This curriculum includes a 4-week course entitled "Principles and Practice of Cancer Prevention and Control." The ultimate goal of this course is to present the most current cancer prevention research to a diverse workforce of researchers and practitioners eager to address the current challenges in this field.

A susceptibility locus on chromosome 6q greatly increases lung cancer risk among light and never smokers.

Cigarette smoking is the major cause for lung cancer, but genetic factors also affect susceptibility. We studied families that included multiple relatives affected by lung cancer. Results from linkage analysis showed strong evidence that a region of chromosome 6q affects lung cancer risk.

Haplotype and cell proliferation analyses of candidate lung cancer susceptibility genes on chromosome 15q24-25.1.

Recent genome-wide association studies have linked the chromosome 15q24-25.1 locus to nicotine addiction and lung cancer susceptibility. To refine the 15q24-25.

Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene.

Purpose: We have previously mapped a major susceptibility locus influencing familial lung cancer risk to chromosome 6q23-25. However, the causal gene at this locus remains undetermined. In this study, we further refined this locus to identify a single candidate gene, by fine mapping using microsatellite markers and association studies using high-density single nucleotide polymorphisms (SNP).

Familial aggregation of common sequence variants on 15q24-25.1 in lung cancer.

Three recent genome-wide association studies identified associations between markers in the chromosomal region 15q24-25.1 and the risk of lung cancer. We conducted a genome-wide association analysis to investigate associations between single-nucleotide polymorphisms (SNPs) and the risk of lung cancer, in which we used blood DNA from 194 case patients with familial lung cancer and 219 cancer-free control subjects.

EGFR-T790M is a rare lung cancer susceptibility allele with enhanced kinase activity.

The use of tyrosine kinase inhibitors (TKI) has yielded great success in treatment of lung adenocarcinomas. However, patients who develop resistance to TKI treatment often acquire a somatic resistance mutation (T790M) located in the catalytic cleft of the epidermal growth factor receptor (EGFR) enzyme. Recently, a report describing EGFR-T790M as a germ-line mutation suggested that this mutation may be associated with inherited susceptibility to lung cancer.

Identification of a novel tumor suppressor gene p34 on human chromosome 6q25.1.

In this study, we observed loss of heterozygosity (LOH) in human chromosomal fragment 6q25.1 in sporadic lung cancer patients. LOH was observed in 65% of the 26 lung tumors examined and was narrowed down to a 2.

The biology of tobacco and nicotine: bench to bedside.

Strong epidemiologic evidence links smoking and cancer. An increased understanding of the molecular biology of tobacco-related cancers could advance progress toward improving smoking cessation and patient management. Knowledge gaps between tobacco addiction, tumorigenesis, and cancer brought an interdisciplinary group of investigators together to discuss "The Biology of Nicotine and Tobacco: Bench to Bedside.

Mutational activation of the MAP3K8 protooncogene in lung cancer.

The MAP3K8 protooncogene (Cot/Tpl-2) activates the MAP kinase, SAP kinase, and NF-kappaB signaling pathways. MAP3K8 mutations occur in the rat homologue, but activating mutations have yet to be identified in primary human tumors. We have identified MAP3K8 as a transforming gene from a human lung adenocarcinoma and characterized a 3' end mutation in the cDNA.

Identifying novel homozygous deletions by microsatellite analysis and characterization of tumor suppressor candidate 1 gene, TUSC1, on chromosome 9p in human lung cancer.

Loss of heterozygosity (LOH) studies indicate that genetic alterations of chromosome 9p occur in numerous tumor types, suggesting the presence of tumor suppressor genes (TSGs) on chromosome 9p critical in carcinogenesis. Our previous LOH analyses in primary lung tumors led us to propose that chromosome 9p harbors other TSGs important in lung tumorigenesis. In this study, 30 non-small-cell lung cancer and 12 small-cell lung cancer cell lines were screened with 55 markers to identify new regions of homozygous deletion (HD) on chromosome 9p.

LOH of chromosome 12p correlates with Kras2 mutation in non-small cell lung cancer.

Previous observation has shown that the wild-type Kras2 allele is a suppressor of lung cancer in mice. Here we report that loss of heterozygosity (LOH) of chromosome 12p was detected in approximately 50% of human lung adenocarcinomas and large cell carcinomas, and Kras2 mutations were detected at codon 12 in approximately 40% of adenocarcinomas and large cell carcinomas. Interestingly, all of the lung adenocarcinomas and large cell carcinomas containing a Kras2 mutation exhibited allelic loss of the wild-type Kras2 allele when a correlation between LOH of the region on chromosome 12p and Kras2 mutation was made.